Targeted multiplex next-generation sequencing: advances in techniques of mitochondrial and nuclear DNA sequencing for population genomics.

Next-generation sequencing (NGS) is emerging as an efficient and cost-effective tool in population genomic analyses of nonmodel organisms, allowing simultaneous resequencing of many regions of multi-genomic DNA from multiplexed samples. Here, we detail our synthesis of protocols for targeted resequencing of mitochondrial and nuclear loci by generating indexed genomic libraries for multiplexing up to 100 individuals in a single sequencing pool, and then enriching the pooled library using custom DNA capture arrays. Our use of DNA sequence from one species to capture and enrich the sequencing libraries of another species (i.

PF-8380 and closely related analogs: synthesis and structure-activity relationship towards autotaxin inhibition and glioma cell viability.

A series of PF-8380 analogs, a recently developed autotaxin inhibitor, was explored. Inhibition of autotaxin by these analogs, as well as by all PF-8380 synthetic intermediates, shows the importance of meta-dichlorobenzyl and benzo[d]oxazol-2(3H)-one fragments. However, analogs 8 and 9, bearing only the benzo[d]oxazol-2(3H)-one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF-8380 and temozolomide (TMZ).

A universal optical all-fiber Omnipolarizer.

Wherever the polarization properties of a light beam are of concern, polarizers and polarizing beamsplitters (PBS) are indispensable devices in linear-, nonlinear- and quantum-optical schemes. By the very nature of their operation principle, transformation of incoming unpolarized or partially polarized beams through these devices introduces large intensity variations in the fully polarized outcoming beam(s). Such intensity fluctuations are often detrimental, particularly when light is post-processed by nonlinear crystals or other polarization-sensitive optic elements.

Demonstration of polarization pulling using a fiber-optic parametric amplifier.

We report the observation of all-optical polarization pulling of an initially polarization-scrambled signal using parametric amplification in a highly nonlinear optical fiber. Broadband polarization pulling has been achieved both for the signal and idler waves with up to 25 dB gain using the strong polarization sensitivity of parametric amplifiers. We further derive the probability distribution function for the final polarization state, assuming a randomly polarized initial state, and we show that it agrees well with the experiments.

Bithiopheneimide-dithienosilole/dithienogermole copolymers for efficient solar cells: information from structure-property-device performance correlations and comparison to thieno[3,4-c]pyrrole-4,6-dione analogues.

Rational creation of polymeric semiconductors from novel building blocks is critical to polymer solar cell (PSC) development. We report a new series of bithiopheneimide-based donor-acceptor copolymers for bulk-heterojunction (BHJ) PSCs. The bithiopheneimide electron-deficiency compresses polymer bandgaps and lowers the HOMOs--essential to maximize power conversion efficiency (PCE).

The diagnostic and biological implications of laminin expression in serous tubal intraepithelial carcinoma.

There is compelling evidence to suggest that serous tubal intraepithelial carcinoma (STIC) is the likely primary site for the development of many pelvic high-grade serous carcinomas (HGSCs). Identifying molecules that are upregulated in STIC is important not only to provide biomarkers to assist in the diagnosis of STIC but also to elucidate our understanding of the pathogenesis of HGSC. In this study, we performed RNA sequencing to compare transcriptomes between HGSC and normal fallopian tube epithelium (FTE), and we identified LAMC1 encoding laminin γ1 as one of the preferentially upregulated genes associated with HGSC.

Convenient solid phase extraction of cephalosporins in milk using a molecularly imprinted polymer.

In this paper, a molecularly imprinted polymer (MIP) for cephalosporin molecules (cephalexin (CFL) and cephapirin (CFP)), was prepared by non covalent molecular imprinting approach and applied to solid phase extraction (SPE). For MIP synthesis, a tributylammonium cefadroxil salt (TBA-CFD) was used as template with methacrylic acid and ethylene glycol dimethacrylate as monomer and cross-linker, respectively, in acetone-methanol 92/8 (v/v) mixture. The selectivity of MIP versus non imprinted polymer (NIP) was confirmed for CFL, CFD and CFP in standard solutions as well as in milk samples.

Differential expression of microRNA species in a freeze tolerant insect, Eurosta solidaginis.

Freeze tolerance in insects is associated with a variety of adaptations including production of cryoprotectants, specialized proteins that regulate ice formation, and energy-saving mechanisms that strongly suppress the rates of metabolic processes in the oxygen-limited frozen state. We hypothesized that microRNAs (miRNAs), small non-coding transcripts that bind to mRNA, could play a role in the global regulation of energy-expensive mRNA translation in frozen insects and would be modulated at subzero temperatures. Expression levels of miRNA species were evaluated in control (5 °C) and frozen (-15 °C) goldenrod gall fly larvae, Eurosta solidaginis, using a miRNA microarray.

Marine turtle mitogenome phylogenetics and evolution.

The sea turtles are a group of cretaceous origin containing seven recognized living species: leatherback, hawksbill, Kemp's ridley, olive ridley, loggerhead, green, and flatback. The leatherback is the single member of the Dermochelidae family, whereas all other sea turtles belong in Cheloniidae. Analyses of partial mitochondrial sequences and some nuclear markers have revealed phylogenetic inconsistencies within Cheloniidae, especially regarding the placement of the flatback.

γ-Secretase modulator in Alzheimer's disease: shifting the end.

The outcomes of the clinical trials of the γ-secretase inhibitor Semagacestat (LY-450139) and the γ-secretase modulator (GSM) Tarenflurbil were disappointing, but may not represent the end of the γ-secretase era. γ-Secretase modulators, by definition, only block the γ-secretase cleavage of amyloid-β protein precursor (AβPP) to generate the longer, 42-residue amyloid-β (Aβ42) without changing the production of total Aβ. The first generation GSMs were shown to block Aβ42 generation while increasing Aβ38.

Development of a carbon-14 labeling approach to support disposition studies with a pegylated biologic.

Although it is widely accepted that one can extend the pharmacokinetic half-life of a therapeutic protein by covalent conjugation with polyethylene glycol (PEG), the disposition properties of such biologics have not yet been fully evaluated. Therefore, a novel [¹⁴C]-labeling method was developed that can be applied to a biologic conjugated with PEG through a maleimide-cysteine reaction. The method was used to study the tissue and tumor distribution of a PEGylated Adnectin, a recombinant protein derived from the 10th type III domain of fibronectin, in nude mice bearing human xenograft tumors.

1H NMR metabolomics analysis of glioblastoma subtypes: correlation between metabolomics and gene expression characteristics.

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by unpredictable clinical behaviors that suggest distinct molecular subtypes. With the tumor metabolic phenotype being one of the hallmarks of cancer, we have set upon to investigate whether GBMs show differences in their metabolic profiles. (1)H NMR analysis was performed on metabolite extracts from a selection of nine glioblastoma cell lines.

An emperor penguin population estimate: the first global, synoptic survey of a species from space.

Our aim was to estimate the population of emperor penguins (Aptenodytes fosteri) using a single synoptic survey. We examined the whole continental coastline of Antarctica using a combination of medium resolution and Very High Resolution (VHR) satellite imagery to identify emperor penguin colony locations. Where colonies were identified, VHR imagery was obtained in the 2009 breeding season.

Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme.

The infiltration of glioma cells into adjacent tissue is one of the major obstacles in the therapeutic management of malignant brain tumours, in most cases precluding complete surgical resection. Consequently, malignant glioma patients almost invariably experience tumour recurrences. Within the brain, glioma cells migrate rapidly either amoeboidly or mesenchymally to invade surrounding structures, in dependence on the extracellular environment.

New development in in-capillary electrophoresis techniques for kinetic and inhibition study of enzymes.

Enzymes are often quantified by measuring their biological activity. Capillary electrophoresis is gaining its position in this field due to the ongoing trend to miniaturize biochemical assays. The aim of this work was to compare pre-capillary (off-line) and in-capillary electrophoresis techniques for studying enzymatic activity.

Nanometer scale assessment of mechanical strain induced in silicon by a periodic line array.

Measuring stress and strain, induced by nanostructures, at the nanometer scale is still a challenge. In this work, we investigate the strain induced by sub-micrometric periodic line arrays deposited on single crystal (001) Si substrate. We study the influence of the lines width and the spacing between the lines for two sets of samples: a silicon nitride lines array and a poly-silicon line array capped with a Si3N4 stressor layer.

[Food environment in childcare settings in Quebec: results from a descriptive study].

Purpose: The goal of this study was to describe different components of the food environment in childcare settings.

Methods: Visits were made to 33 early childcare centres (CPEs) in the Estrie region of Quebec, Canada. Data were collected between March and July 2008 using a questionnaire based on the Cohen model.

Incorrect radiographic evaluation after vascularized bone grafting for scaphoid fracture or nonunion.

Purpose: The present study is a review of patients with scaphoid non-unions treated with a dorsal vascularized bone graft. The study highlights a subset of patients incorrectly diagnosed as graft failures.

Methods: A retrospective review of patients who received vascularized grafts for scaphoid nonunions was performed over a four-year period.

Structures of adnectin/protein complexes reveal an expanded binding footprint.

Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin (¹⁰Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three ¹⁰Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23.

The growth response to androgen receptor signaling in ERα-negative human breast cells is dependent on p21 and mediated by MAPK activation.

Introduction: Although a high frequency of androgen receptor (AR) expression in human breast cancers has been described, exploiting this knowledge for therapy has been challenging. This is in part because androgens can either inhibit or stimulate cell proliferation in pre-clinical models of breast cancer. In addition, many breast cancers co-express other steroid hormone receptors that can affect AR signaling, further obfuscating the effects of androgens on breast cancer cells.

Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer.

Claudins are integral tight junction proteins that are responsible for maintaining the integrity of epithelial cell architecture and cell polarity. Claudin-3 and -4 are overexpressed in several cancers and have been shown to act as receptors for the Clostridium perfringens enterotoxin (CPE), a toxin that causes rapid cell lysis. CPE has demonstrated effectiveness in treating several different cancers in mouse models, provided that these cancers express claudin-3 or claudin-4.

Perceptions of employed parents about early childhood obesity and the need for prevention strategies.

Responses to the increased prevalence of childhood obesity are merging, and employed parents will become targets for strategies designed to prevent childhood obesity. This study aimed at describing their perceptions of employed parents about childhood obesity and determining which prevention strategies they would need the most. In this cross-sectional study, 504 employed parents were recruited from 33 child care centers in Sherbrooke (Quebec, Canada) who completed a self-administered questionnaire on their perceptions about childhood obesity and the need for prevention strategies.

Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin.

Background: Resistance to current chemotherapeutic agents is a major cause of therapy failure in ovarian cancer patients, but the exact mechanisms leading to the development of drug resistance remain unclear.

Methods: To better understand mechanisms of drug resistance, and possibly identify novel targets for therapy, we generated a series of drug resistant ovarian cancer cell lines through repeated exposure to three chemotherapeutic drugs (cisplatin, doxorubicin, or paclitaxel), and identified changes in gene expression patterns using Illumina whole-genome expression microarrays. Validation of selected genes was performed by RT-PCR and immunoblotting.